6533b7ddfe1ef96bd1274032
RESEARCH PRODUCT
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
Daria BulanovaAleksandr IanevskiAndrii BugaiYevhen AkimovSuvi KuivanenHenrik PaavilainenLaura KakkolaJatin NandaniaLaura TurunenTiina OhmanHanna Ala-hongistoHanna M PesonenMarika S KuismaAnni HonkimaaEmma Louise WaltonValentyn OksenychMartina B. LoreyDmitry GuschinJungmin ShimJinhee KimThoa T ThanSo Young ChangVeijo HukkanenEvgeny KulesskiyVarpu S MarjomakiIlkka JulkunenTuula Anneli NymanSampsa MatikainenJani S SaarelaFamara SaneDidier HoberGulsah GabrielJef K De BrabanderMiika MartikainenMarc P WindischJi-young MinRoberto BruzzoneTero AittokallioMarkus Vaha-koskelaOlli VapalahtiArto PulkVidya VelagapudiDenis Kainovsubject
0301 basic medicinevirusesFAMILY INHIBITORSlcsh:QR1-502Virus Replicationlcsh:Microbiologychemistry.chemical_compoundTranscription (biology)SALIPHENYLHALAMIDEhost responseTRANSCRIPTIONprogrammed cell deathinnate immunity1183 Plant biology microbiology virologySulfonamidesAniline CompoundsapoptosisTransfection3. Good healthInfectious DiseasesProto-Oncogene Proteins c-bcl-2X-L INHIBITORVirus DiseasesvirustauditVirusesRNA ViralBiologyTransfectionta3111Antiviral AgentsArticleCell LineMicrobiology in the medical areaantiviral agent03 medical and health sciencesohjelmoitunut solukuolemaVirologyMikrobiologi inom det medicinska områdetHumansMetabolomicsBenzothiazolesInnate immune systemapoptosis; antiviral agent; innate immunity; host responseZIKA VIRUS-INFECTIONCHRONIC LYMPHOCYTIC-LEUKEMIAPOTENTta1183INFLUENZA-Ata1182RNAIsoquinolinesVirology030104 developmental biologyViral replicationchemistryCell cultureApoptosisCELLSREPLICATIONDNA Viral3111 BiomedicineDNAdescription
Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases. © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-09-25 |